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UNDERSTANDING MASS SPECTRA Second Edition UNDERSTANDING MASS SPECTRA: A Basic Approach SECOND EDITION R Martin Smith A JOHN WILEY & SONS, INC., PUBLICATION Copyright # 2004 by John Wiley & Sons, Inc All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400, fax 978-646-8600, or on the web at www.copyright.com Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008 Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose No warranty may be created or extended by sales representatives or written sales materials The advice and strategies contained herein may not be suitable for your situation You should consult with a professional where appropriate Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages For general information on our other products and services please contact our Customer Care Department within the U.S at 877-762-2974, outside the U.S at 317-572-3993 or fax 317-572-4002 Wiley also publishes its books in a variety of electronic formats Some content that appears in print, however, may not be available in electronic format Library of Congress Cataloging-in-Publication Data: Smith, R Martin Understanding mass spectra : a basic approach – 2nd ed / R Martin Smith p cm Includes bibliographical references and index ISBN 0-471-42949-X (acid-free paper) Mass Spectrometry I Title QD96 M3S65 2005 5430 0873–dc22 2004003683 Printed in the United States of America 10 CONTENTS Preface to the Second Edition xi Acknowledgments xv Abbreviations and Notations Used in This Book Instrumentation 1.1 1.2 1.3 1.4 xvii Introduction / 1.1.1 Overview / 1.1.2 Sample Introduction / Ionization Source / 1.2.1 Electron Ionization Source / 1.2.2 Chemical Ionization / 1.2.3 Other Ionization Methods / 1.2.3.1 Electrospray Ionization / 1.2.3.2 Desorption Ionization / 12 m/z Analysis / 13 1.3.1 Time-of-Flight (TOF) / 13 1.3.2 Magnetic Sector / 15 1.3.3 Transmission Quadrupole / 17 1.3.3.1 Selected Ion Monitoring (SIM) / 21 1.3.4 Quadrupole Ion Trap (QIT) / 22 1.3.5 Other Types of Mass Analysis / 24 1.3.5.1 Mass Spectrometry/Mass Spectrometry(MS/MS) / 24 1.3.5.2 Accurate m=z Analysis / 26 1.3.6 Spectral Skewing / 26 Ion Detection / 30 1.4.1 Electron Multiplier / 32 1.4.2 Photomultiplier Detector / 33 v vi CONTENTS 1.5 Data System / 33 1.5.1 Instrument Tuning and Calibration / 33 1.5.2 The Mass Spectrum / 37 1.5.2.1 Production of the Mass Spectrum / 37 1.5.2.2 Terminology: Ions vs Peaks / 41 1.5.3 Library Searches / 41 1.5.4 Using the Data System to Analyze GC/MS Data / 45 1.6 Criteria for Good-Quality Spectra / 50 Additional Problems / 51 Mass Spectrometric Resources on the Internet / 52 References and Suggested Reading / 53 Elemental Composition from Peak Intensities 2.1 56 Natural Isotopic Abundances / 56 2.1.1 Atomic and Molecular Mass / 59 2.1.2 Calculated Exact Masses and Mass Defects / 60 2.2 Determining Elemental Composition from Isotope Peak Intensities / 64 2.2.1 One or More Atoms of a Single Element / 64 2.2.1.1 Chlorine and Bromine / 64 2.2.1.2 Ion Designation and Nomenclature / 70 2.2.1.3 Probability Considerations with Multiple Numbers of Atoms / 71 2.2.1.4 Isotope Peak Intensity Ratios for Carbon-Containing Ions—The X þ Peak / 74 2.2.1.5 A, A þ 1, and A þ Elements / 77 2.2.1.6 Isotope Peak Intensity Ratios for Carbon-Containing Ions—The X þ Peak / 78 2.2.1.7 Overlapping Peak Clusters—Contributions from 13 C Only / 80 2.2.1.8 Silicon / 82 2.2.2 Complex Isotope Clusters / 83 2.2.2.1 Sulfur Dioxide / 83 2.2.2.2 Diazepam / 86 2.3 Obtaining Elemental Compositions from Isotope Peak Intensities / 89 Examples / 91 Additional Problems / 96 References / 98 CONTENTS Ionization, Fragmentation, and Electron Accounting vii 99 3.1 3.2 3.3 3.4 3.5 3.6 A Brief Review of Orbitals and Bonding / 99 Even- and Odd-Electron Species / 101 Site of Initial Ionization / 103 Types of Fragmentation / 107 The Nitrogen Rule / 109 Energy Considerations in Fragmentation Processes / 110 3.6.1 Fragmentation Rates / 110 3.6.2 Metastable Ions / 112 3.6.3 Energy Diagrams / 113 3.6.4 Stevenson’s Rule / 116 Additional Examples / 117 Problems / 119 References / 120 Neutral Losses and Ion Series 121 4.1 Neutral Losses / 121 4.1.1 Losses from the Molecular Ion / 121 4.1.2 Loss of Small Molecules from Aromatic Ions / 126 4.2 Low-Mass Ion Series / 131 4.2.1 n-Alkane Spectra / 132 4.2.2 Effect of Chain Branching on the Spectra of Aliphatic Hydrocarbons / 134 4.2.3 Ion Series for Nonaromatic Compounds / 136 4.2.4 Aromatic Ion Series / 142 4.2.5 Use of Ion Series: Mass Chromatograms / 145 Additional Problems / 148 References / 148 A Rational Approach to Mass Spectral Problem Solving 150 5.1 Guidelines for Solving Mass Spectral Problems / 150 Examples / 153 Problems / 161 Reference / 163 a-Cleavage and Related Fragmentations 6.1 6.2 Introduction / 164 Benzylic Cleavage / 166 164 viii CONTENTS 6.3 Cleavage Next to Aliphatic Nitrogen / 170 6.3.1 Structural Relationships: a-Cleavage in 1-Phenyl-2-aminopropanes / 171 6.3.2 Cleavage Next to Electron-Deficient Nitrogen / 176 6.3.3 a-Cleavage in Complex Nitrogenous Ring Systems / 179 6.4 Cleavages of Aliphatic Oxygenated Compounds / 180 6.4.1 a-Cleavage / 180 6.4.2 Bond Cleavage Away from the Ionization Site / 184 6.4.3 Cleavage at Carbonyl Groups / 186 6.5 Elimination Fragmentations in Oxygen and Nitrogen Compounds / 192 6.5.1 Secondary Elimination from Initial a-Cleavage Ions / 192 6.5.2 Hydride Shifts / 195 6.5.3 Elimination Fragmentations of Some Aromatic Compounds / 196 6.5.4 Water Elimination in Aliphatic Alcohols / 198 Examples / 200 Additional Problems / 202 References / 206 Important Mass Spectral Rearrangements / 207 7.1 7.2 Introduction / 207 g-Hydrogen Rearrangement / 208 7.2.1 McLafferty-Type Rearrangement / 208 7.2.2 g-Hydrogen Rearrangement in Alkylbenzenes / 213 7.2.3 g-Hydrogen Rearrangement Initiated by a Remote Ionization Site / 217 7.3 Cyclohexanone-Type Rearrangement / 223 7.4 Retro Diels–Alder Fragmentation / 228 7.5 Double-Hydrogen (McLafferty þ 1) Rearrangement / 234 Additional Problems / 236 References / 237 Rationalizing Mass Spectral Fragmentations 8.1 8.2 8.3 8.4 238 General Guidelines / 238 Loss of Small Molecules / 241 8.2.1 Loss of Small Molecules from Aromatic Ions Revisited / 241 8.2.2 g-Butyrolactone / 243 Ephedrine / 246 Ortho Effect: The Hydroxybenzoic Acids / 251 CONTENTS ix Additional Problems / 254 References / 256 Structure Determination in Complex Molecules Using Mass Spectrometry 257 9.1 9.2 9.3 Introduction / 257 ‘‘Designer Drugs’’ Related to MDA / 258 Cocaine and Its Metabolites / 262 9.3.1 Peak Correlations / 263 9.3.2 Proposed Fragmentations / 268 9.3.3 Application / 271 9.4 Phencyclidine and Its Analogs / 274 9.4.1 Fragmentations of Phencyclidine / 274 9.4.2 Phencyclidine Analogs / 282 9.5 A Practical Problem / 284 References / 285 10 Answers to Problems Index 287 353 PREFACE TO THE SECOND EDITION Mass spectrometry (MS) has undergone a profound change over the past decade Instrumentation and techniques related to the automated analysis of biomolecules and new drugs now account for a large percentage of the research and publications in this field In comparison, gas chromatography/mass spectrometry (GC/MS) and electron ionization (EI) mass spectra of ‘‘small’’ molecules play a less important role than they once did But GC/MS is far from dead, and EIMS continues to be the ionization method of choice for many laboratories that routinely analyze volatilizable low molecular mass compounds such as drugs, flavor and odor components, pesticides, and petroleum products This situation seems unlikely to change in the near future The interpretation of EI mass spectra has always been a challenging subject to learn and to teach—especially to individuals who have not had the benefit of a graduate education in chemistry or who have been out of college for several years The challenge is compounded by manufacturer-encouraged reliance on library search results for compound identification Why learn anything about spectral interpretation when the computer can all the work? The answer to this question is simple, as most conscientious users quickly realize The library search often does not provide a realistic answer or (worse) may provide an answer that looks correct but is not Even software programs that profess to ‘‘interpret’’ unknown spectra can only provide probable answers After that, you are left to your own devices It was tempting to substantially increase the breadth and depth of the material that was covered in the first edition However, my experience has been that an encyclopedic presentation of mass spectral interpretation does not give beginning mass spectrometrists what they need, which is a presentation that provides a few fundamental concepts in a logical, organized manner, without distracting and unnecessary detail I wrote and revised this book for beginning mass spectrometrists, and I have retained the simplicity of its approach for that reason My own understanding of mass spectral interpretation has developed, and continues to develop, by trial and error I am admittedly mostly self-taught My knowledge of mass spectral literature has been limited by the nature of my career, whose primary focus was forensic science, not mass spectrometry Some will see that as a xi 358 INDEX Curran, D.P., 54 Current, electron multiplier output, 33, 34, 35, 38–39, 41, 46 Cyanoacetylene, loss of, 311 Cycloheptatrienyl (tropylium) ion, 128–129, 241–242, 249–250 See also Benzyl ion, equilibrium with cycloheptatrienyl ion Cycloheptenyl ions, 241, 249–250 Cyclohexane, 31, 106 1,2-dimethyl-, 139 N,N-dimethylamino-, 226, 227 methoxy-, 226, 227 Cyclohexanol, 4-methyl-, 227, 330 Cyclohexanone, 119, 224, 224–226, 298, 340 2-(2-chlorophenyl)-2-(N-methylamino)-, see Ketamine deuterium-labeled derivatives, 223–224 Cyclohexanone-type rearrangement, 207, 223–227, 279, 284, 330, 331, 334, 347, 349 deuterium labeling and, 223–224 modified, 340–341 Cyclohexene, 106 derivatives, retro Diels-Alder fragmentation and, 228–232, 334, 335 3-hydroxy-, 234, 331–332 4-hydroxy-, 234, 331 1-methyl-4-(2-propenyl)-, see Limonene 1-phenyl-, 280, 347 3-phenyl-, 230, 231–232 4-phenyl-, 230, 231 Cyclohexylamine, 93 Cycloo¨ ctenyl ions, 241 Cyclopentadiene, 243 hexachloro-, 72, 289–290, 291 Cyclopentadienyl ion, 128–129, 242, 243 Cyclopentane, 1-ethyl-1-methyl, 139 Cyclopropane, 1-pentafluorobenzamido2-phenyl, 83 Cyclopropenium ion, 128–129, 225, 242 DAC, see Digital-to-analog converter Dalton, definition, Damico, J.N., 54 Data System, 33–49 library searches and, 41–44 tuning and calibration and, 33–37 use in analysis of GC/MS data, 1, 29, 46–49, 146 ‘‘Date rape drug,’’ 243 dc generator, see Generator, dc Decahydroquinoline N,7-dimethyl-, 228, 331 N-methyl, 228, 331 n-Decane, 131, 132, 156 de Hoffman, E., 24, 54 Deniz, A.A., 129, 148 Denton, M.B., 21, 55 Derivative formation; see also Deuterium labeling, use in determining fragmentation mechanisms use in molecular mass determination, 152 use in structure determination, 262ff ‘‘Designer drugs,’’ 261 Desorption ionization, 4, 10, 12–13 Detection limit of mass spectrometry, see Threshold for ion detection Detector electron multiplier, see Electron multiplier detector flame ionization, 46 Mass Selective, see Mass Selective Detector photodiode array, 16 photographic plate, 16 photomultiplier, 16, 33 Deuterium labeling, use in determining fragmentation mechanisms, 209–212, 223–225, 258, 263, 276–278, 284–285, 349–352 Dewar benzene, see Bicyclo[2.2.0]hexa-2,5diene 1,4-Diazabenzene, 160, 161 Diazepam, 284, 285, 349, 350–352 deuterated derivative, 284, 285, 349–350 molecular ion peak cluster analysis, 86–89 2,2-Dicyanoethane, 1-(o-chlorophenyl)-, see Propionitrile, 2-cyano-3(o-chlorophenyl)-N,NDicyclohexylamine, 236, 237, 334 Diels-Alder reaction, 228 N,N-Diethylamphetamine, see Amphetamine, N,N-diethylDiethylether, 203, 321, 322 N,N-Diethyl-1-phenylcyclohexylamine, see Phencyclidine, N,N-diethyl analog Digital-to-analog converter, 35 1,1-Dimethoxyethane, 181, 182, 182–183, 190 Dimethylisopropylamine, 327 Dimethylsulfone, 163, 308, 309 INDEX Diphenylmethane, 167, 184 Di-n-propylamine, 193, 194 Diradical, as fragmentation product, 102, 278, 279, 280 Distonic ion, 102, 225, 235–236, 244, 280 DNA fragments, analysis by MS, 3, 14 Double bond, definition, 101 formation in fragmentation product, see Olefin elimination Double-charged ions, see Ionization, multiple Double-focusing mass spectrometer, 17, 26 Double hydrogen (McLafferty þ 1) rearrangement, 207, 234–236 Doxepin, 204, 324 Drug Enforcement Administration (DEA), 276 Duhaime, R., 286 Dwell time, in selected ion monitoring, 22 Dynode, 32 Ecgonine methyl ester, 263, 265, 346 aroyl derivatives, see Cocaine benzoyl ester, see Cocaine cinnamoyl ester, 45 phenylacetyl ester, see Phenylacetylmethylecgonine propylated aroyl esters, 275, 344–346 toluyl ester, see Toluylmethylecgonine ethyl ester, aroyl derivatives, see Cocaethylene propyl ester, benzoyl ester, 273, 274 hydroxymethoxybenzoyl ester, 275, 344–346 propyloxybenzoyl ester, 275, 344–346 propyloxymethoxybenzoyl ester, 275, 344–346 ‘‘Ecstasy’’, see 3,4Methylenedioxymethamphetamine Efficiency, ionization, 6, 30 Ehleringer, J.D., 58, 98 EIMS, see Electron ionization mass spectrometry Electron aperture, Electron ionization mass spectrometry, 2, 4, See also Ionization, electron Electron ionization source, 4, 5–8 ion lifetimes and, 111, 114, 281 359 maintenance, 8, 34 Electron multiplier detector, 15, 16, 32–33 setting gain, 33, 34 Electron volt (eV), definition, Electronegativity, charge stabilization and, see Charge stabilization, electronegativity and ionization and, 104–105, 176, 178 Electrospray ionization, 4, 9–12, 24, 44, 54, 152 Electrostatic analyzer in double-focusing mass spectrometer, 17 Elemental composition determination from exact mass, 62–63, 263 from isotope peak intensity ratios, 52, 64ff examples, 91ff guidelines for, 89–91 use in solving mass spectral unknowns, 151, 152–153 End caps in quadrupole ion trap, 22–23 Energy diagrams, see Fragmentation, energy diagrams Energy, free, see Free energy of activation (ÁGz) Enthalpy of activation (ÁHz), 111–112, 116 Entropy of activation (ÁSz), 111–112, 115 effect of ring size in transition state on, 112, 207, 240 Ephedrine, 10, 246, 247–250 Equation, mass spectrometric for magnetic sector analyzer, 16 for quadrupole ion trap, 22 for time-of-flight spectrometer, 14 for transmission quadrupole, 20 Error arithmetic, in structure determination, 239 experimental, in peak intensity measurement, 76, 82, 88, 214, 291 ESI, see Electrospray ionization Esters aliphatic a-cleavage and, 187–189 McLafferty rearrangement and, 188, 211–212, 221, 234–236 aromatic a-cleavage and, 187–189, 196, 323, 324, 338 ketene loss by, 196–197, 338–339 Ethane, 102–103 1-bromo-1-chloro-2,2,2-trifluoro-, see Halothane 360 INDEX Ethers aliphatic, a-cleavage and, 165, 181–183, 297, 321–322 See also Alcohols, aliphatic, a-cleavage and secondary elimination after a-cleavage and, 192–195, 321–322 relative importance of vs amines, 192, 322 weak molecular ion peaks and, 181 aromatic C-O bond cleavage and, 184–185, 314–315, 340 formaldehyde elimination and, see Formaldehyde, loss by phenylmethylethers olefin elimination and, 197–198, 345 Ethoxybenzene, olefin elimination and, 197, 198 Ethylene loss of, see Alpha-cleavage, secondary elimination after; Ethoxybenzene, olefin elimination in; Gammahydrogen rearrangement; Olefin elimination; Retro Diels-Alder fragmentation 1,2-dichloro-, 64, 65, 66 Ethylisopropylamine, 327 Ethylisopropylether, 192, 194 N-Ethyl-3,4-methylenedioxyamphetamine (‘‘MDE’’), see 3,4-MethylenedioxyN- ethylamphetamine, N-Ethyl-1-phenylcyclohexylamine, see Phencyclidine, N-ethyl analog Eugenol, 185, 186, 314 ‘‘Eve,’’ see 3,4-Methylenedioxy-N-ethylamphetamine Even-electron ions, 103 decomposition of, 108, 110 Excited state, Extractor plate, 5, Fales, H.M., 10, 54 Fast-atom bombardment (FAB), 4, 13 Fast GC, 29–30 Fenn, J.B., 10 FID, see Detector, flame ionization Filament, 5, 8, 13, 24, 32, 35, 46 Fire debris, analysis by mass chromatography, 145–146 Fishhook (single-headed arrow), 102, 109, 119, 120 Fishman, V.N., 37, 54 Fluorine, as A þ element, 77 Focusing plate, ion, see Ion focusing plate Ford, V.L., 98 Formaldehyde, 108 elimination of, 244–245, 297 loss by phenylmethylethers, 131, 184, 314 Formamide, 102 Forward library search, 42 Fragmentation, see also specific fragmentation reactions, such as Alphacleavage, etc.; Neutral losses; Olefin elimination; Rearrangement charge-migration, see Charge-migration fragmentation; Heterolytic cleavage charge-retention, see Charge-retention fragmentation; Homolytic cleavage charge stabilization and, see Stevenson’s rule conjugation, effects of, see Fragmentation mechanisms, resonance stabilization and energy diagrams, 113–116 entropy factors and, 112, 115, 207, 240 free energy of activation (ÁGz) and, 111–112, 113–116, 134, 135, 142–143, 180, 281, 349 intra- vs intermolecular, 2, 8–9, 56, 240 ion lifetimes and, 111, 112–113, 114, 281 kinetic factors in, 110–112 olefin formation and, see Olefin elimination product ion stability and, 105–107, 132, 136, 240 See also Alpha-cleavage, product ion stability and; Stevenson’s rule product olefin structure and, 216, 302, 316, 319 product radical stability and, 133, 136, 240 See also Alpha-cleavage, product radical stability and rates, 111–112 thermodynamic factors in, 110–111 types, 107–109 Fragmentation mechanisms from peak correlations, 209–211, 223–225, 263–271, 276–281, 349–352 guidelines for rationalizing, 238–241 initial ionization site and, 108–109, 239–240 resonance stabilization and, 105–106, 116, 119, 166, 184–185, 190, 213, INDEX 216–217, 225, 231, 235, 240, 241, 248, 254, 270, 283, 319, 329, 332 See also Alpha-cleavage, initiated by remote ionization site; Gammahydrogen rearrangement, initiated by remote ionization site ring size for transition states and, 112, 207, 240 Free energy of activation (ÁGz), 111–112, 113–116 See also Fragmentation, free energy of activation and Furan, 2-acetoxymethyl, 188, 189, 206, 329 2-Furancarboxylic acid, propyl ester, 203, 323 2-Furanmethanethiol, 118, 119 z ÁG , see Free energy of activation Gagne´ , H.M., 206 Gain, detector, 33, 34 Gamma-hydrogen (g-hydrogen) rearrangement, 153, 207ff in alkylbenzenes, 213–216, 218, 321 competition with a-cleavage, 216 minimal alkyl size for, 216, 219, 259 in 1-phenyl-2-aminopropanes, 259–261 initiated by remote ionization site, 217–219 McLafferty-type, 188, 190, 191, 208–213, 223, 234 aliphatic carboxylic acid derivatives and, 211–212, 213, 220–222, 234, 330 deuterium labeling and, 209–211 ketones and, 209–212, 329–330 structural requirements for, 208 Gas chromatography, 50, 152 compound separation by, 1, 3, 17, 29 retention times, compound identification and, 43, 152, 336 Gas chromatography/mass spectrometry, 35, 126 block diagram, carrier gases in, 3, 32 data, computer analysis of, 46–50, 145–146 specificity of, 2, 336 spectral skewing and, 26–28 Gasoline, evaporated, mass chromatograms, 146 GBL, see g-Butyrolactone GC/MS, see Gas chromatography/mass spectrometry 361 Generator ac, use with quadrupole ion trap, 23, 24 dc in quadrupole ion trap, 23, 24 in transmission quadrupole, 17–18, 21 RF in quadrupole ion trap, 22, 23 in transmission quadrupole, 17–18, 21, 25 GHB, see Butyric acid, g-hydroxyGinger, oil of, 142 Gooding, K.M., 206 Goodwin, M., 205, 206 Graves, G.R., 98 ÁHz, see Enthalpy of activation Halothane, 127, 299–300, 301 Hansson, R.C., 149 Harmine, 256, 339–340 Harrison, A.G., 54 Helium as carrier gas in GC/MS, 3, 32 as damping gas in quadrupole ion trap, 24 Henchman, M., 21, 54 n-Heptane, 137, 300, 302 2-methyl-, 135, 301 Heptanoic acid, ethyl ester, 211, 212 Hertel, R.H., 55 Heterolytic cleavage, 108–109, 117, 119, 164, 172, 231 See also Chargemigration fragmentation Hexamethyldisilane, 141 Hexane 2-methyl-, 31, 300, 303 3-methyl-, 300, 303 3,3,4-trimethyl-, 147, 302 2-Hexanone, McLafferty rearrangement in, 330 3-Hexanone, 156, 157 3-Hexene-(Z), 147, 302 n-Hexylamine, 193, 194 High-mass peaks, importance in spectral interpretation, 42, 121, 134, 153, 240 High-performance liquid chromatography/ mass spectrometry, 2, 3, 4, 10, 11, 21, 54 High resolution mass spectrometry, 17, 20, 24, 258, 263 See also m/z Analysis, accurate High vacuum, use in mass spectrometry, 2, 4, 362 INDEX Highest Occupied Molecular Orbital (HOMO), 103, 105 Holmes, J.L., 134, 148, 233, 237 Holmes, R.T., 98 Holzer, G., 148 Homolytic cleavage, 108–109, 114, 116, 117, 119, 164, 172 See also Chargeretention fragmentation HPLC/MS, see High-performance liquid chromatography/mass spectrometry Hu¨ ckel’s Rule, 129, 158 Hydride shifts, 195–196 Hydrocarbons aliphatic, 132–136, 138, 145, 146, 300, 304 branched, 134–136, 300–303 aromatic, 128, 131–132, 133, 142–144, 145–146, 166–168, 213–216, 295, 303, 310–311 olefinic, 138–140, 302 saturated cyclic, 138–140 Hydrogen radical, loss in a-cleavage, see Alphacleavage, hydrogen radical loss in; Benzylic cleavage, hydrogen radical loss via radical, loss from o-position of aromatic ring, 278–279, 283, 349–350 rearrangement, see Rearrangement, hydrogen See also Olefin elimination use as carrier gas in GC/MS, 3, 32 Hydrogen chloride, 64, 65 Hydrogen cyanide, 106, 107, 108 electronic structure, 126 elimination of, 122–123, 126, 129, 158, 160, 161, 242, 307–308, 311–312, 326 Hydroxybenzoylecgonine, see Benzoylecgonine, arylhydroxy derivative Hydroxybenzyl ion, 249–250 Hydroxycocaethylene, see Cocaethylene, arylhydroxy derivative Hydroxycocaine, see Cocaine, arylhydroxy derivative Hydroxymethoxycocaethylene, see Cocaethylene, arylhydroxymethoxy derivative Hydroxymethoxycocaine, see Cocaine, arylhydroxymethoxy derivative N-Hydroxy-3,4Methylenedioxyamphetamine, see 3,4-Methylenedioxyamphetamine, N- hydroxyIbogaine, 209, 210 Ibuprofen, 336 Infrared spectrometry, 1, 33, 49 Intensities isotope peak, see Isotope peak intensities mass spectral peak, 41 concentration dependence in GC/MS, see Spectral skewing error in measuring, see Error, experimental, in peak intensity measurement Intensity, weighted, for library searches, 42 Intermediate, reaction, definition, 111–112 Internet resources for mass spectrometry, 52–53 Intra- vs intermolecular fragmentation, 2, 8–9, 56, 240 Ion distonic, see Distonic ion even-electron, see Even-electron ions intermediate not observed in spectrum, 114, 248, 279, 281, 351 lifetimes, detectability and, 111–114, 281 metastable, 112–113 molecular, see Molecular ion multiple-charged, 6, 7, 39, 103, 129–130, 289 nomenclature, 70–71 odd-electron, see Odd-electron species, ions precursor, 25, 113, 134, 155, 192, 239 product, 26, 113, 134, 192, 239 radical, see Odd-electron species, ions stability, fragmentation and, see Fragmentation, product ion stability and Ion detection, 16, 30, 32–33 See also Detector Ion focusing plate, 5, Ion-molecule reactions, in chemical ionization mass spectrometry, 8–9, 56 Ion series, low mass, see Low mass ion series Ion source, see Electron ionization source Ion trap analyzer, see Quadrupole ion trap Ionization chemical, see Chemical ionization mass spectrometry INDEX electron, 2, 4, 6–7, 101–105 efficiency of, 6, 30 molecular orbitals and, 103–105 multiple, 6, 7, 39, 103, 129–130, 289 site of initial, 103–107, 165, 239–240 pulse, 13, 24, 29 resonance electron capture, Ionization energy (ionization potential), 6, 105 table, 106 use in determining ionization site, 105–107, 117–119 use in determining site of charge in product ions, see Stevenson’s rule IR, see Infrared spectrometry Isoamyl acetate, 235, 236 Isobutane, as reagent gas in chemical ionization MS, 9, 10 Isobutyl alcohol, 203, 321–322 Isobutylamine, 322 Isoprene, loss of, 229, 232 Isopropanol, see 2-Propanol Isopropyl chloride, see Propane, 2-chloroIsotope, definition, 58 Isotope abundances, 52, 53, 56–59 Isotope peak intensities, 64ff, 152–153 A, A þ 1, and A þ elements and, 77–78 bromine and chlorine, 64–74 carbon-containing compounds, 74–76, 78–79 elemental composition from, see Elemental composition, from isotope peak intensity ratios for ions having two or more elements, 68–69, 77, 83–89 internet calculators for, 52–53 molecular ion peak cluster, analysis, 76, 79, 80–82, 83–85, 86–89 normalization of, 90, 91, 93, 151, 293 overlapping peak clusters and, 80–82, 85–89, 95–96, 296 probabilities and, 66–74 silicon, 82–83 sulfur, 83–85 X þ peak, 76, 77–78, 90, 151 determining number of carbons from, 76 for carbon-containing compounds, 74–76 X þ peak, 78–79, 91, 151 See also Isotope peak intensities, bromine and chlorine 363 Kataoka, H., 12, 54 Ketamine, 256, 340–341 Ketene, loss of, 188, 196–197, 206, 329, 338–339 Keto-enol tautomerization, 131, 241, 243, 249–250 Ketones a-cleavage and, 157, 186, 243, 298, 321, 329–330 McLafferty rearrangement and, 209–212, 330 Kinetic control of reactions, 111–112 Kinter, M.T., 286 Komer, K.B., 286 Kwok, K.-S., 45, 54 Laser desorption ionization (LDI), matrix-assisted (MALDI), 4, 12–13, 14 Lawson, G., 54 LC/MS, see High performance liquid chromatography/mass spectrometry Leary, J.J., 21, 54 LeChatlier’s principle, 243 LECO, 14, 30, 31 Lemon, odor of, see Limonene Lias, S.G., 54, 98, 148 Library, mass spectral internet, 53 evaluation of, 44, 50, 54, 55 NIST/EPA/NIH, 46 Library search, 41–46 mass spectral problem solving and, 151, 170, 341 match index in, 42–43 PBM, see Probability Based Matching Lidocaine, 176 Limonene, 142, 229, 230, 232 Linclau, B., 54 Lodge, B.A., 278, 286 Loh, M.J., 98 Loh, S.Y., 55 Lorazepam, 70 Lord, H.L., 54 Losses, neutral, see Neutral losses Low mass ion series, 136–145 alkanes, 136–138, 145, 302, 304 alkenes, 138–139, 145, 302 alkylsilanes, 141 alpha-cleavage, 138, 140–141, 175, 302, 326, 329 364 INDEX Low mass ion series (Continued) aromatic, 138, 142–145, 160, 171, 213–214, 302, 305, 307, 309, 310, 312, 325, 328, 333, 338 benzoyl, 128, 138, 144–145, 148, 263, 267, 271, 303–304, 335 benzyl, 128, 138, 143–144, 171, 213–214, 241–242, 302–303, 310, 320 carboxylic acid derivatives, 141 cycloalkanes, 138, 141–142, 145 ketones vs alkanes, 156–157, 304, 329 mass spectral problem solving and, 151, 153 mass chromatography and, 145–146 monoterpenes, 141–142 phencyclidine analogs, 283, 347 Lysergic acid diethylamide (LSD), 233, 332 M þ peak intensities, see Isotope peak intensities, X þ peak M þ peak intensities, see Isotope peak intensities, X þ peak m/z Analysis, 13–26 accurate, 26 ion elemental compostions from, 26, 62–63, 263, 264–267 quadrupole ion trap and, 26 mass defects and, 62–63 m/z Discrimination (ÁM), 20, 26, 34, 37–38, 41, 61, 64, 68, 77, 78, 81, 86 sensitivity and, 21, 26, 33, 34, 63–64 tuning and, 33–34 MacMurray, P., 286 Magnet, collimating, 5–6 Magnetic sector analyzer, 15–17 accurate m/z analysis and, 17, 26 MALDI, see Laser desorption ionization, matrix-assisted March, R.E., 22, 55 Marijuana, see Á9-Tetrahydrocannabinol; Cannabidiol Mass exact, 60–64 atomic, table, 52 internet calculators for, 53 elemental composition and, 62–63, 263 molecular, 59, 151 determination by chemical ionization, 9, 152 determination by electrospray ionization, 11, 152 relation to number of nitrogen atoms and, see Nitrogen rule monoisotopic, 59, 60, 87 nominal, 61–62 units, See also u (Unified atomic mass unit) Mass chromatography, 29–31, 49, 50 comparison with selected ion monitoring, 49, 146 forensic arson analysis and, 145–146 Mass defect (Á), 60–62, 68, 84 Mass Selective Detector (MSD), 21 Mass spectrometer, see also m/z Analysis, Magnetic sector analyzer, Quadrupole ion trap, Time-of-flight m/z analyzer, Transmission quadrupole as GC detector, 29, 30, 46–47, 145–146 calibration, see Calibration double-focusing, 17, 26 high vacuum in, sample introduction modes for, 3–4 tuning, see Tuning Mass spectrometry chemical ionization, see Chemical ionization mass spectrometry high resolution, see High resolution mass spectrometry See also m/z Analysis, accurate negative ion, 6, tandem, see Mass spectrometry/mass spectrometry Mass spectrometry/mass spectrometry, 9, 11, 24–26, 54, 258 quadrupole ion trap and, 24, 26 Mass spectrum, 37–41 base peak in, see Base peak criteria for acceptable, 50–51, 83, 126, 292, 299 molecular ion peak in, see Molecular ion, peak predicting, from spectra of related compounds, 258, 271–273, 284, 347 representations, 39–41 visual examination, importance of, 42–43, 50–51, 151 Match index, 42, 44, 45, 151 McLafferty, F.W., 42, 45, 53, 55, 68, 98, 108, 109, 120, 121, 141, 148, 208, 235, 237 McLafferty rearrangement, see Gammahydrogen rearrangement, McLaffertytype ‘‘McLafferty þ 1’’ rearrangement, see Double hydrogen rearrangement INDEX MDA, see 3,4-Methylenedioxyamphetamine MDE, see 3,4-Methylenedioxy-Nethylamphetamine MDMA, see 3,4Methylenedioxymethamphetamine Mechanism, fragmentation, see Fragmentation mechanisms Mescaline, see b-Phenethylamine, 3,4,5-trimethoxyMetastable ions, 112–113 Methamphetamine, 54, 172, 173, 174, 175–176, 177, 195, 202, 246, 247, 248, 249, 250, 312–314, 320, 321 a-cleavage in, 173–174, 247, 312–313 condensation product, see N-(1-Phenyl-2methylaminopropyl)-1-phenyl-2-(Nmethylamino)propane Methane, 56, 57, 58 as reagent gas in chemical ionization mass spectrometry, 8–9 Methcathinone, 246, 247, 248–249, 250, 335–336 Methyl carbenium ion, 102–103 radical, 102–103, 145, 155 electronic structure of, 102–103 loss from polymethylated benzenes, 166, 168, 311 loss from within aromatic rings, 143, 145, 158, 307 Methyl acetate, 188, 189 Methyl benzyl ketone, see 2-Propanone, 1-phenylMethyl bromide, 64, 65, 71 Methyl tert-butylamine, 326–327 Methyl 2,5-dimethylbenzoate, see Benzoic acid, 2,5-dimethyl-, methyl ester Methyl 3,5-dimethylbenzoate, see Benzoic acid, 3,5-dimethyl-, methyl ester Methyl ethylether, 201 Methyl isopropylether, 203, 321–322 Methyl n-propylether, 183, 203, 321–322 Methyl vinyl ketone, see 3-Buten-2-one Methyldiethylamine, 205, 326–327 Methylecgonine, see Ecgonine, methyl ester 3,4-Methylenedioxyamphetamine (‘‘MDA’’), 47, 48, 49, 54, 258, 259, 260, 261 N,N-dimethyl-, 262, 341–343 N-ethyl-, see 3,4-Methylenedioxy-Nethylamphetamine N-hydroxy-, 47, 48, 49–50 365 N-methyl-, see 3,4Methylenedioxymethamphetamine 3,4-Methylenedioxy-N-ethylamphetamine (MDE), 259, 260, 261, 341 3,4-Methylenedioxymethamphetamine (MDMA), 44, 54, 259, 260, 261 N-formyl derivative, 179, 180 1-(3,4-Methylenedioxyphenyl)-2aminopentane, 342 1-(3,4-Methylenedioxyphenyl)-2aminopropane, see 3,4Methylenedioxyamphetamine 1-(3,4-Methylenedioxyphenyl)-N,2dimethyl-2-aminopropane, 342 1-(3,4-Methylenedioxyphenyl)-N-isopropylb-phenethylamine, 342 1-(3,4-Methylenedioxyphenyl)-2-methyl-2aminobutane, 342 1-(3,4-Methylenedioxyphenyl)-3-methyl-2aminobutane, 342 1-(3,4-Methylenedioxyphenyl)-N-methyl-Nethyl-b-phenethylamine, 342 1-(3,4-Methylenedioxyphenyl)-2propanone, oxime, 47, 48, 49–50 1-(3,4-Methylenedioxyphenyl)-1-propene, 47, 48 1-(3,4-Methylenedioxyphenyl)-N-propyl-bphenethylamine, 342 a-Methylfentanyl, 204, 324 2-Methyl-1-propanol, see Isobutyl alcohol Mikaya, A.I., 54, 98, 148 Miller, P.E., 21, 55 Milne, G.W.A., 54 Molecular ion, 6, 7, 102, 103–104 composition of, see Elemental Composition; Isotope peak intensities; Nitrogen rule losses not allowed from, 122, 152, 159, 181–182, 288 peak absence in spectrum, 9, 11, 111, 113, 141, 151, 159, 181–182, 248 determining presence in spectrum, 122, 151–152 intensity of, in spectra of aromatic compounds, see Aromatic compounds, intense molecular ion peaks and rearrangement of, prior to bond cleavage, 134, 140, 141 rings plus double bonds in, formula, 91, 151, 153 stability of, 113–114, 142 366 INDEX Molecular orbitals, see Orbitals, molecular Molecular weight, 59, 61 Molecules, protonated, in chemical ionization mass spectrometry, 9, 25, 152 Mollah, Y.A., 148 Morpholine, N-(1-phenylcyclohexyl)-, see Phencyclidine, morpholine analog MS/MS, see Mass spectrometry/mass spectrometry MS Search (NIST software), 46, 53 Multiple ionization, see Ionization, multiple Myrcene, 142 n-orbitals, see Orbitals, nonbonding Naphthalene, 106, 128, 133, 143, 146 1-methyl-, 133 National Institute for Standards and Technology, 29, 46, 53 Needle, nebulizing (in electrospray ionization), 10, 11 Negative ion mass spectrometry, see Mass spectrometry, negative ion Neopentane, see Propane, 2,2-dimethylNeutral losses, 53, 121–123, 126, 128–131, 151, 152, 153, 239, 240, 241–243 See also specific fragmentations such as Acetylene, elimination of; Hydrogen Cyanide, elimination of; Ketene, loss of; Olefin elimination; and Rearrangement by alkanes, 132–134 by aromatic compounds, 126, 128–131, 143, 145, 241–243 forbidden, 122, 152, 159, 181, 288 molecular ion peak and, see Molecular ion, peak, determining presence in spectrum use in mass spectral problem solving, 151–153 Neutral species diradical, 102, 278, 279, 280 even-electron, 101–102 radical, 102–103 Nicotinamide, 205, 325, 326 Nigam, I.C., 233, 237 NIST, see National Institute for Standards and Technology Nitrobenzene, 97, 293, 294 Nitrogen, as A þ element, 77 as drying gas in electrospray ionization, 10 charge stabilization by, 107, 165, 170, 175, 176, 180, 190, 191, 248, 268, 278, 281, 340 elemental composition and, 77, 78, 90 See also Nitrogen rule isotope peak intensities, 86–89, 93, 292, 293, 307–308 isotopic abundances, 58 molecular (N2) electronic structure, 126 elimination of, 106, 107, 108, 126 Nitrogen oxides, loss of O from, 122, 123 Nitrogen rule, 90, 109–110, 151, 152, 210 examples, 93, 157, 160, 209, 292, 293, 307 ionic mass and, 109–110 NMR, see Nuclear magnetic resonance spectrometry Nominal mass, 61–62 n-Nonane, 161, 304 n-Nonanoic acid, 211, 212 Nonbonding orbitals, see Orbitals, nonbonding Norbornene, see Bicyclo[2.2.1]hept-2-ene Norcocaine, 263, 265, 266 N-trideuteriomethyl-, 263, 266 Normalization of peak intensities, see Isotope peak intensities, normalization of Norman, K.W., 149 Nortriptyline, 178, 179 N-pentafluroropropionyl derivative, 178, 179 Nowicki, J., 145, 149 Nuclear magnetic resonance spectrometry, Number of carbon atoms, relation to X þ peak intensity, see Isotope peak intensities, X þ peak, determining the number of carbon atoms from  (Symbol for electrical neutrality), 101 8-Octadecenamide, 223, 330 n-Octane, 134, 135, 156 Octanoic acid, methyl ester, 211, 212 4-Octene, 139 Odd-electron species ions, 101, 102 decomposition of, 107–108 peaks in spectrum representing, 109–110, 153, 209, 330, 333 radicals, 102–103 relative stability of, 132, 136, 240 INDEX Olefin elimination; see also Neutral losses; Rearrangement p-bond formation as driving force in, 108, 112, 134, 197, 208, 242, 245, 269 from primary aliphatic ions, 134, 199, 225–226 in g-hydrogen rearrangements, see Gamma-hydrogen rearrangement in McLafferty rearrangements, see Gamma-hydrogen rearrangement, McLafferty type in phenylalkylethers, see Ethers, aromatic, olefin elimination and in retro Diels-Alder fragmentations, see Retro Diels-Alder fragmentation in secondary elimination after a-cleavage, see Alpha-cleavage, secondary elimination after ketene loss, see Ketene, loss of product olefin structure and, 216, 302 Orbitals p, 101, 103–104, 105 s, 101, 103–104, 105 antibonding (p* and s*), 103–104 atomic, 99–100 molecular, 101, 103–104, 105 highest occupied (HOMO), 103, 105 site of initial ionization and, 104–105 nonbonding (n), 101, 103–104, 158, 165, 239 subhybrid, 99–100 Ortho effect, 217, 251–254, 308, 310, 338–339 Oxygen atomic, loss of, 122, 123, 309 charge stabilization by, 117, 119, 165, 180, 183, 190, 199, 243, 244, 253 isotope peak intensities, 77–78, 91 examples, 79, 87–89, 92, 220, 293, 296, 297, 306, 308, 337 isotopic abundances, 58 p-Bond formation, fragmentation and, see Olefin elimination, p-bond formation as driving force in ‘‘P–2-P’’, see 2-Propanone, 1-phenyl Palmitic acid, butyl ester, see Butyl palmitate Papaver somniferum, 184 Papaverine, 183, 184–185 Pascal’s triangle, binomial expansion and, 74, 75 367 Pawliszyn, J., 54 PBM Search, see Probability Based Matching PCP, see Phencyclidine Peak, mass spectral, 37–39, 41 Peak correlations, applications, 271–272, 284, 347–348 cocaine, 263–268 diazepam, 284–285, 349–352 fragmentation mechanisms from, see Fragmentation mechanisms, from peak correlations phencyclidine, 276–281 n-Pentanal, 191 Pentane, 155 2,2-dimethyl-, 300–302, 303 2,3-dimethyl-, 31, 300–302, 303 2,4-dimethyl-, 137, 300–302 3,3-dimethyl-, 137, 300–302 3-ethyl-, 300–302, 303 2,2,3-trimethyl-, 135, 136 Pentanoic acid, 221, 222 n-Pentanol, 198, 199, 200 3-Pentanol, 140, 195 2-Pentanone, 209, 210–212 deuterium-labeled derivatives of, 210–212 McLafferty rearrangement and, 209–212 3-methyl-, 222, 329–330 4-methyl-, 330 3-Pentanone, 140 n-Pentylamine, 198 3-Pentylamine, 140, 141, 195 Peppers, Capsicum (hot), 185; see also Capsaicin Perfluorokerosene, as calibration standard, 37 Perfluorotri-n-butylamine, 3, 33, 34, 37, 51, 52, 125, 287–288 Peters, K.S., 148 Petroleum distillates, analysis of, 145–146 Peyote, see b-Phenethylamine, 3,4,5-trimethoxy-, PFTBA, see Perfluorotri-n-butylamine Pharmaceuticals, analysis by electrospray ionization MS, 11 Phenanthrene, 128, 133 Phencyclidine (‘‘PCP’’), 143, 274ff, 276, 347, 349 analogs, 282–284, 347–349 arylmethyl analogs, 277, 278, 279 benzyl analog, 284, 349 cyclohexanone-type rearrangement and, 279–280 368 INDEX Phencyclidine (‘‘PCP’’) (Continued) deuterium-labeled derivatives, 276–281 N,N-diethyl analog, 284, 347, 348 N-ethyl analog, 282 hydrogen radical loss by, 278–279, 280, 281, 283 low mass ion series, 283, 347 morpholine analog, 282, 283, 347 peak correlations, 276ff, (table) 277 retro Diels-Alder fragmentation and, 278, 280 thiophene analog, 282, 283, 347 thiophene morpholine analog, 284, 347–348, 349 o-toluyl analog, 277, 278, 279 b-Phenethylamine, 200, 201, 202 N,N-dimethyl-, 177, 312–314 N-ethyl-, 177, 312–314 N-methyl-, 147, 302 3,4,5-trimethoxy-, 175 Phenol, 129, 130, 131, 243 2,6-dichloro-, 163, 309, 310 o-, m-, and p-methoxy-, 186, 187, 314–315 Phentermine, 172, 173, 174, 175, 177, 312–314 N,N-dimethyl-, 175 Phenyl ion, 105–106, 128, 129 radical, 105 Phenylacetylmethylecgonine, 271, 272, 273, 343 1-Phenyl-2-aminobutane, 177, 312–314 1-Phenyl-2-aminoethane, see b-Phenethylamine 1-Phenyl-2-aminopropane, see Amphetamine 1-hydroxy-, see Cathine 2-methyl-, see Phentermine N-(1-Phenylcyclohexyl)morpholine, see Phencyclidine, morpholine analog 1-Phenylcyclohexylpiperidine, see Phencyclidine 1-Phenyl-3,3-dimethylbutane, 215, 216 1-Phenyl-1,2-dimethylpropane, 215, 216 1-Phenyl-2,2-dimethylpropane, see Benzene, neopentyl1-Phenyl-2-(N-methylamino)propane, see Methamphetamine 1-hydroxy-, see Ephedrine 1-Phenyl-2-(N-methylamino)-1-propanone, see Methcathinone N-(1-Phenyl-2-methylaminopropyl)-1phenyl-2-(N-methylamino)propane, 195, 315–320 1-Phenyl-2-methylbutane, 215 1-Phenyl-3-methylbutane, 215, 216 Phenylmethylethers, see Benzene, methoxy-; Formaldehyde, loss by phenylmethylethers 1-Phenyl-2-methylpropane, see Benzene, isobutyl 1-Phenyl-2-propanone, see 2-Propanone, 1-phenyl1-Phenyl-1,2,2-trimethylpropane, 215, 216 Pheromone canine, 205, 206 insect, 163, 309 Photodiode array detector, 16 Photographic plate detector, 16 Photomultiplier detector, 16, 33 Phthalic acid, esters, 254 Piperidine N-(1-benzylcyclohexyl)-, see Phencyclidine, benzyl analog N-pentyl-, 203, 323 1-phenylcyclohexyl-, see Phencyclidine Plate extractor, see Extractor Plate ion focusing, see Ion Focusing Plate Poles (in transmission quadrupole), 17, 18, 20 Poppy, opium, 184 Poquette, M.A., 286 Potential, see Ionization energy; Voltages Precursor ion, see Ion, precursor Probabilities, 66 binomial expansion and, 73–74 isotope peak intensities and, 66–69, 71 Probability Based Matching, 42, 43, 55 Probe, heated, 3–4 Problems, solving mass spectral chemical history and, 151, 308, 309, 312, 320, 336 examples, 153ff guidelines for, 150–153 isotopic peak intensities and, 152–153 See also Intensities, isotope peak library searches and, 151 low mass ion series and, 137, 153 See also Low mass ion series neutral losses and, 121–123, 153 See also Neutral losses Nitrogen rule and, 152 See also Nitrogen rule INDEX Product ion mass spectrometry/mass spectrometry, 25–26 Propane, 2,2-dimethyl-, 154, 155 2-chloro-, 119, 298 n-Propanol, 226 2-Propanol, 117, 200, 201 2-Propanone, see Acetone 1-cyclohexenyl-, 204, 323 1-phenyl-, 202, 320, 321 Propene, loss of, 194, 198, 345 Propionic acid, 2-(p-isobutylphenyl)-, see Ibuprofen Propionitrile, 2-cyano-3-(o-chlorophenyl), 170, 312 Propyl radical, loss, cyclohexanone-type rearrangement and, 223, 225, 279, 334 n-Propylamine, 119, 298 Propylecgonine, see Ecgonine, propyl ester Proteins, analysis by MS, 3, 11, 14 Protonated molecules, 9, 25 Pseudococaine, 286 Pseudomolecular ion, Pulse ionization, 13, 24, 29 2H-Pyran, tetrahydro-, 98, 296, 297 Pyrazine, see 1,4-Diazabenzene Pyridine, 129, 130, 242 3-bromo-, 96, 292, 293 4-methoxy-, 162, 307, 308 4-methyl-, N-oxide, 123 2-propyl-, 216, 217 4-propyl-, 216, 217 3-Pyridinecarboxamide, see Nicotinamide Pyrrole, 157, 158 q (variable in quadrupole MS), see a and q Quadrupole ion trap, 13, 22–24, 29, 55 high resolution mass spectra from, 24, 26 MS/MS using, 24, 26 scan direction in, 24, 287 Quadrupole analyzer, see Transmission quadrupole Quality of spectra, criteria for, 50–51, 83, 126 Radical ions, see Odd-electron species, ions neutral, 6, 7, 102–103 See also Oddelectron species, radicals stability, fragmentation and, see Fragmentation, product radical stability and 369 Radical site induced fragmentation, see Homolytic cleavage Radio frequency generator, see Generator, RF Reagent gas, in chemical ionization mass spectrometry, 8–10, 57 Rearrangement p-bond formation and, see Olefin elimination, p-bond formation as driving force in cyclohexanone-type, see Cyclohexanonetype rearrangement double-hydrogen, see Double-hydrogen rearrangement hydride, see Hydride shifts hydrogen (general), 240; see also Olefin elimination 3-center, examples, 145, 158, 247, 269 4-center, examples, 131, 145, 181, 218, 219, 241, 243, 249, 252, 278, 297, 328, 329, 332, 334 See also Alpha-cleavage, secondary elimination after; Ethers, aromatic, olefin elimination and; Ethylene, loss of; Formaldehyde, loss by phenylmethylethers; Hydride shifts; Ketene, loss of; Olefin elimination, from primary aliphatic ions 5-center, examples, 235, 236, 341 6-center, examples, 253, 338, 352 See also Alcohols, aliphatic, water elimination from; Cyclohexanone-type rearrangement; Gamma-hydrogen rearrangement 7-center, example, 271 ease of, 240 g-hydrogen, see Gamma-hydrogen rearrangement ketene loss by aromatic compounds, see Ketene, loss of McLafferty, see Gamma-hydrogen rearrangement, McLafferty-type McLafferty þ 1, see Double hydrogen rearrangement olefin elimination, see Olefin elimination product ion stability and, see Fragmentation, product ion stability and; Stevenson’s rule product olefin structure and, 216, 302 ring size of transition state and, 112, 207, 240 370 INDEX RECI, see Resonance electron capture ionization Reconstructed ion chromatography, see Mass chromatography Reconstructed total ion current chromatogram (RTICC), 46, 47, 146, 169, 274 Regnier, F., 206 Remote ionization site, initiation of fragmentation by, see Alpha-cleavage, initiated at remote ionization site; Gamma-hydrogen rearrangement, initiated at remote ionization site; Retro Diels-Alder fragmentation, initiated at remote ionization site Repeller, 5, Resolution chromatographic, peak intensities and, see Spectral skewing m/z (resolving power), 20 See also High resolution mass spectrometry; m/z Discrimination Resonance stabilization, fragmentation mechanisms and, see Fragmentation mechanisms, resonance stabilization and Resonance ejection, with quadrupole ion trap, 24 Resonance electron capture ionization, Retro Diels-Alder fragmentation, 153, 207, 228–233, 331–332, 333, 334, 335, 347 charge-retention and charge-migration mechanisms, 229, 231, 232, 331, 332, 334 initiated at remote ionization site, 232 Reverse Nier-Johnson geometry in high resolution mass spectrometer, 17 Ring size for rearrangement transition states, entropy factors in, 112, 207, 240 Ring electrode, in quadrupole ion trap, 22, 23 Rings plus double bonds, formula, 91, 151, 153 Roboz, J., 55 Rods, quadrupole, see Poles (in transmission quadrupole) RTICC, see Reconstructed total ion current chromatogram Rubenstein, D.R., 58, 98 s-bond cleavage, 102, 108, 132, 136, 156, 164 ÁSz, see Entropy of activation Salicylic acid, see Benzoic acid, 2-hydroxySample introduction, modes for mass spectrometry, 3–4 Saunders, R.A., 148, 206, 256 Scan direction, 17, 28, 287 lines, in stability diagrams, 19–21 range, 14, 17, 21, 24, 35 relation to base peak in spectrum, 39 rates, 14, 26, 29, 35, 45 Schmidt, R.L., 21, 54 Schwartz, M., 256 Scott, D.R., 42, 55 Secondary elimination from a-cleavage ions, see Alpha-cleavage, secondary elimination after Selected ion monitoring (SIM), 21–22 mass chromatography, comparison, 49, 146 mass defects and, 63–64 Self-Training Interpretive and Retrieval System (STIRS), 45, 54 Sensitivity effect of m/z discrimination on, 21, 26, 33, 34, 63–64 pulse ionization and, 14 selected ion monitoring and, 63–64 tuning and, 33–34 Shapiro, R.H., 263, 266, 286 Silanes, alkyl, 147 Silicon isotope peak intensities, 82–83, 94 isotopic abundances, 58 SIM, see Selected ion monitoring Smith, P.J., 286 Smith, R.M., 145, 149, 219, 237, 263, 266, 286 Snyder, G.J., 149 Soft ionization, 9, 11, 24 Software, mass spectral general, 52 interpretive, 45–46, 54, 55 Somayajula, K.V., 54 Source, ion, see Electron ionization source Sparkman, O.D., 54, 69, 98, 110, 120, 148 Spectral skewing, over chromatographic peaks in GC/MS, 24, 26–29 Spectral variation, see Error, experimental, in peak intensity measurement Stability diagram (a vs q plot), for quadrupole ion trap, 23–24 for transmission quadrupole, 19–21 INDEX Stability of ions and radicals, 133, 136, 239, 240 See also Fragmentation, product ion stability and; Fragmentation, product radical stability and Stauffer, D.A., 45, 55 Steele, C., 21, 54 Steeves, J.B., 172, 206 Stein, S.E., 42, 49, 54, 55, 98, 148 Steroids, mass spectra of, 121, 257, 258 Stevenson, D.P., 117, 120 Stevenson’s rule, 116–117, 126, 186, 231, 232, 240, 245 examples, 117–119, 298, 331 STIRS, see Self-Training Interpretive and Retrieval System Styrene, 106, 230, 231 Sulfide, sec-butylisopropyl, 204, 323 Sulfides, aliphatic, a-cleavage and, 166, 204, 323 Sulfur charge stabilization by, 283, 309, 323, 349 isotope peak intensities, 77, 78, 84–85, 93–94, 308–309 isotopic abundances, 58 Sulfur dioxide, 84, 85 Tabernanthe iboga, 180 Tanaka, K., 10 Tandem mass spectrometry, see Mass spectrometry/mass spectrometry Tchekhovskoi, D.V., 54, 98, 148 Tear gas, 168 Terpenes, ion series, 141, 142 Á9-Tetrahydrocannabinol, 39–41, 61, 63, 218, 232 g-hydrogen rearrangement in, 217–219 peak cluster intensities, 76, 79, 98, 297 trimethylsilyl derivative, 63 Á9-Tetrahydrocannabivarin, 218, 219 THC or Á9-THC, see Á9-Tetrahydrocannabinol Thermodynamic control of reactions, 110–111 1-(2-Thienyl)cyclohexylmorpholine, see Phencyclidine, thiophene morpholine analog 1-(2-Thienyl)cyclohexylpiperidine, see Phencyclidine, thiophene analog Thiols, aliphatic, a-cleavage and, 166 Thiophene, 93–94 Threshold for ion detection, 22, 30–31, 41 371 TIC, see Chromatogram, reconstructed total ion current Tick, Lone Star, 163, 309 Tighe, T., 256 Time-of-flight (TOF) mass spectrometer, 12, 13–15, 26, 29, 54 TNT, see Trinitrotoluene Todd, J.F.J., 54 Toluene, 80–82, 143, 144 o-Toluylcyclohexylpiperidine, see Phencyclidine, o-toluyl analog Toluylmethylecgonine, 273, 343 Total ion chromatogram, see Chromatogram, reconstructed total ion current Transition state, definition, 111–112 Transmission quadrupole, 13, 17–21, 26, 34, 36, 37, 54, 55 triple (QQQ), 25–26 See also Mass spectrometry/mass spectrometry Tranthim-Fryer, D.J., 126, 149 Triethylamine, 193, 195 Trifluoromethyl carbenium ion (þCF3), 125, 287, 300, 301 Trimethylbenzenes, 166–167, 168, 311 Trimethylsilyl derivatives, 63, 82 Trinitrotoluene, 254 Triple quadrupole, see Quadrupole mass analyzer, triple; Mass spectrometry/ mass spectrometry Tropane, derivatives of, 266, 268 See also Cocaine Tropylium ion, see Cycloheptatrienyl ion Tuning, 33–35 Turecˇ ek, F., 53, 68, 98, 106, 109, 120, 121, 141, 148, 235, 237 Tuross, N.C., 98 Tylenol, 196 u (Unified atomic mass unit), 3, 60 Ultraviolet spectrometry (UV), 33 Unsaturations, number of , see Rings plus double bonds, formula Vacuum, see High vacuum Valium, see Diazepam Van der Hart, W.J., 140, 149 Venkataraghavan, R., 54 Villwock, R.D., 55 Vinyl carbenium ion, 307 radical, loss of, 122, 123, 160, 314 372 INDEX Voltages accelerating magnetic sector analyzer, 15–16 time-of-flight analyzer, 13–14 electron multiplier, 32–33, 34 ion source, 5, 8, 34 in quadrupole ion trap, 21, 22–24 in transmission quadrupole, 17–21, 22, 25, 35, 36, 37 Vose, J., 243, 256 Waldbauer, J.R., 98 Wallace, J.R., 145, 149 Water, elimination of, 121, 122, 198–200, 223, 321–322 Watson, J.T., 54, 110, 120 Web sites, 29, 46, 52–53 Weighting factor, in library searches, 42 Wesdemiotis, C., 55 Williamson A.E., 148, 206, 256 Wine, gamma-butyrolactone in, 243, 256 Winkler, H.U., 54 Wolcoff, P., 148 X þ peak intensities, see Isotope peak intensities, X þ peak X þ peak intensities, see Isotope peak intensities, X þ peak Yinon, J., 149 Zaikin, V., 54, 98, 148 Zamecnik, J., 286 Zhang, Q.W., 148 Zhu, D., 54, 98, 148 [...]... into the mass spectrometer The mass spectrometer ionizes analyte molecules, then separates and detects the resulting ions The computer system controls the operation of the chromatograph and the MS, and provides data manipulation and storage during and after data collection For volatile samples, gas chromatography (GC) is Understanding Mass Spectra: A Basic Approach, Second Edition By R Martin Smith ISBN... system of the mass spectrometer Helium (He) and hydrogen (H2) are good choices as carrier gases for GC/MS work because their extremely low atomic and molecular masses (4 u and 2 u, respectively; 1 u ¼ 1 unified atomic mass unit2) fall below those of all the ions normally seen in organic mass spectrometry HPLC has become increasingly important as an option for sample separation prior to mass spectral analysis—especially... peak with m/z value at, higher than, or lower than that of the molecular ion peak by a specified number of units Positively charged molecular ion Difference in mass or m/z values (mass or m/z discrimination) Molecular mass Mass spectrometry Mass- to-charge ratio Odd-electron ion Probability ( 1) that an event will occur Quadrupole ion trap Reconstructed total ion current chromatogram Selected ion monitoring... is useful for determining the molecular mass of compounds that do not produce a detectable Mþ by EIMS (see Figure 1.3), CI mass spectra may show an insufficient number of fragment ion peaks to yield structural information The protonated molecules produced during CIMS can be induced to undergo fragmentation by combining CI with product-ion mass spectrometry /mass spectrometry (MS/MS; see Section 1.3.4.1)... detected in mass spectrometry Until fairly recently, volatile compounds were ionized primarily in the electron ionization (EI) source, which is still the most common ion source used in GC/MS work Since the focus of this book is the interpretation of EI mass spectra, most of this section will describe the EI source As the number of larger and less volatile molecules requiring analysis by mass spectrometry... Molecular ionization methods in mass spectrometry Type of Ionization Ionizing Agent Source Pressure Uses Electron ionization (EI) 50–70 eVelectrons 10À4–10À6 torr Chemical ionization (CI) Gaseous ions $1 torr Extensive fragmentation allows structure determination; GC/MS (Section 1.2.1) Molecular mass determination; GC/MS (Section 1.2.2) Molecular mass and structures of high mass, nonvolatile compounds... neutral molecule (product c) This molecular ion (Mþ) is very important because it has virtually the same mass as that of the analyte molecule (the small mass of the lost electron can be ignored) Indeed, mass spectrometry is one of the few analytical tools available for determining the molecular mass of a compound Ion products d and e in Table 1.2 are formed by unimolecular dissociation of Mþ In the... Biopolymers such as peptides may have charge states of þ10 or more from protonation of basic sites on the molecule Since mass spectrometry actually measures the mass- tocharge ratio (m/z) of an ion, not its mass, an ion having a charge greater than þ1 is found not at the m/z value corresponding to its mass (m), but rather at m/2, m/3, or m/4, depending on the number of charge states Further, if m is not evenly... consistency regarding the terms used for the atomic mass unit The single term amu was used at one time, but it had different definitions in physics and chemistry, both involving 16 O as a standard mass This term was discontinued when a unified standard mass was adopted The International Union of Pure and Applied Chemistry (IUPAC) suggests the unified atomic mass unit (abbreviated u), which is based on 12C... Reflectron time-of-flight (TOF) mass spectrometer (Adapted with permission Copyright LECO Corporation, St Joseph, MI) Solving for m/z leads to the mass spectrometric equation governing TOF mass spectrometry: m=z ¼ 2Vt2 =D2 ð1:1Þ In Equation 1.1, D is fixed by instrument design and V can be held constant electronically, so that m/z is proportional to the square of the travel time t The mass spectrum is collected